Myasthenia gravis with anti-muscle-specific tyrosine kinase antibodies during therapy for multiple myeloma: a case report.

BACKGROUND: The onset of myasthenia (MG) gravis with anti-muscle-specific tyrosine kinase (MuSK) antibodies most commonly peaks in the fourth decade of life, and MG with MuSK antibodies (MuSK-MG) rarely coexists with a malignant tumor. To date, MuSK-MG has not been reported in multiple myeloma (MM). CASE PRESENTATION: A 60-year-old male with MM who was receiving treatment with bortezomib and thalidomide presented diplopia, ptosis, and limb weakness. A diagnosis of MM with Bence-Jones proteinuria was established when he was 56 years old, and he received chemotherapy with four courses of bortezomib and dexamethasone. Although he received thalidomide as maintenance therapy, it was discontinued a year before hospital admission because of sensory neuropathy as a side effect. Six months before hospital admission, he developed mild diplopia. One month before admission, his chemotherapy was interrupted because of viral infection and fatigability. Then he developed neck weakness and bilateral ptosis. A diagnosis of MuSK-MG was made based on neurological and serological examinations. According to the previous relevant literature, this is the first report of MuSK-MG in a patient with MM. CONCLUSIONS: In patients with MM, the possibility of co-existing of autoimmune disease, including MuSK-MG, should be considered. This case emphasizes the need to still consider testing for anti-MuSK antibodies in older MM patients where there is clinical suspicion for possible MG despite negative anti-acetylcholine receptor antibodies and lacking classic MuSK MG phenotype at onset.

Health-related quality of life among community-dwelling patients with intractable neurological diseases and their caregivers in Japan.

AIMS: The aims of this study were: (i) to clarify the general quality of life (QOL) of patients with intractable neurological disease; (ii) to clarify the general QOL of the caregivers of these patients; and (iii) to explore the association of QOL in patient-caregiver pairs. METHODS: A cross-sectional survey was conducted between November 2003 and May 2004 among community-dwelling patients diagnosed with Parkinson's disease (PD), spinocerebellar degeneration (SCD), multiple system atrophy (MSA), and amyotrophic lateral sclerosis (ALS) and their caregivers using a mailed, self-administered questionnaire. To measure QOL, we used the Medical Outcome Study 36-Item Short Form (SF-36) for patients and the short form of the health-related QOL scale SF-36 (SF-8) for caregivers. RESULTS: A total of 418 questionnaires were analyzed. For the patients, all of the general QOL domains of the SF-36 were significantly lower than the national standard value for all of the diagnoses. Physical function, role physical, and role emotional domains were also low. For caregivers, all of the QOL summary scores of the SF-8 for all diagnoses were significantly lower than the national standard value. Although there were several significant correlations of QOL between patients and caregivers, overall the correlations were low. CONCLUSIONS: Support for patients with neurological diseases and their caregivers is needed in order to maintain physical and mental QOL.

Care burden and depression in caregivers caring for patients with intractable neurological diseases at home in Japan.

OBJECTIVES: The aims of this study are to describe the care burden on caregivers of individuals with intractable neurological diseases and to clarify the prevalence of depression in caregivers and factors related to the presence of depression. METHODS: A cross-sectional survey was conducted among caregivers who provide home care to patients with neurological diseases such as Parkinson disease (PD), spinocerebellar degeneration (SCD), multiple system atrophy (MSA), and amyotrophic lateral sclerosis (ALS), using a mailed, self-administered questionnaire. We used the Burden Index of Caregivers to measure multi-dimensional care burden and the Center for Epidemiologic Studies Depression scale to determine the presence of depression among caregivers. RESULTS: A total of 418 questionnaires were analyzed. Although several domains of care burden for caregivers were significantly different among the four diseases, the intensity of caregiving and hours spent caregiving were the main definitive variables. In addition, we described different aspects of the care burden using the multi-dimensional care burden scale. The prevalence of depression in caregivers was high (PD, 46%; SCD, 42%; MSA, 63%; ALS, 61%). Hours required for close supervision of the patient (P=0.015), intensity of caregiving (P=0.024), and low household income (P=0.013) were independently-related variables for depression in caregivers. CONCLUSIONS: The care burden of caregivers was mainly explained by the intensity of caregiving and hours spent caregiving per day, not only according to the disease. The high prevalence of depression indicates the need for effective interventions, especially for caregivers of patients with MSA and ALS.

[A case of suspected neuromyelitis optica spectrum disorder preceded by aseptic meningitis-like symptoms].

A 20-year-old woman was hospitalized after experiencing headaches, high fever, and nausea for 1 week. She was conscious and had no abnormal neurological findings or neck stiffness. Examination of her cerebrospinal fluid showed a pronounced elevation of mononuclear cells. She was admitted to our hospital with the diagnosis of meningitis and had hypersomnia 3 days later. Brain MRI (FLAIR) demonstrated high-intensity lesions at the dorsal pons, and bilateral hypothalamus and spinal MRI demonstrated longitudinal T2 high-intensity lesions extending from C2 to C4 and from C6 to Th6. We suspected neuromyelitis optica spectrum disorder (NMOSD) and administered intravenous methylprednisolone after which her symptoms and MRI abnormalities improved immediately. Serum anti-aquaporin-4 antibody and anti-myelin oligodendrocyte glycoprotein antibody were negative. Thus, it is important to perform MRI imaging early in the onset of aseptic meningitis due to numerous case reports of patients diagnosed with neuromyelitis optica or NMOSD with initial meningitis-like symptoms.

Neuro-Sweet disease: report of the first autopsy case.

BACKGROUND: Neuro-Sweet disease is a rare condition of central nervous involvement accompanied by cutaneous Sweet lesions. Neuropathological changes in neuro-Sweet disease are unknown. OBJECTIVE: To describe post-mortem findings of the first case of neuro-Sweet disease. RESULTS: A 44-year-old Japanese man developed recurrent episodes of cerebral and brainstem encephalitis with cutaneous Sweet lesions from the age of 34 years. His HLA typing was B54 and Cw1, and the symptoms and MRI abnormalities markedly subsided following corticosteroid therapy. Histologically, there were multiple lesions of perivascular cuffing of small venules by macrophages without vasculitis in the thalamus, temporal lobe, basal ganglia, pons, leptomeninges or ventricular ependym. CONCLUSIONS: The core neuropathological findings were: perivascular cuffing around particularly small veins; absence of granulomatous or necrotic angitis; mainly macrophage infiltration; and the thalamus being most affected. In the present case, the diagnosis of neuro-Sweet disease was made by skin biopsy 5 years after the onset of the central neuron system symptoms. We should pay more attention to skin lesions in steroid responsive recurrent encephalitis in patients who are HLA-B54 or Cw1 positive.

Validation of the Burden Index of Caregivers (BIC), a multidimensional short care burden scale from Japan.

BACKGROUND: We constructed a concise multidimensional care burden scale that reflects circumstances unique to Japan, with a focus on intractable neurological diseases. We surveyed 646 family caregivers of patients with intractable neurological diseases or stroke using 28 preliminary care burden scale items obtained from qualitative research. The results were used to finalize the feeling of care burden scale (BIC: burden index of caregivers), and verify its reliability and validity. METHODS: The survey was conducted among caregivers providing home health care to patients with intractable neurological diseases (PD [Parkinson's disease], SCD [spinocerebellar degeneration], MSA [multiple system atrophy], and ALS [amyotrophic lateral sclerosis]) or CVA (cerebrovascular accident) using a mailed, self-administered questionnaire between November, 2003 and May, 2004. RESULTS: Response rates for neurological and CVA caregivers were 50% and 67%, respectively, or 646 in total (PD, 279; SCD, 78; MSA, 39; ALS, 30; and CVA, 220). Item and exploratory factor analyses led to a reduction to 11 items, comprising 10 items from the 5 domains of time-dependent burden, emotional burden, existential burden, physical burden, and service-related burden; and 1 item on total burden. Examination of validity showed a moderate correlation between each domain of the BIC and the SF-8 (Health related quality of life scale, Short Form-8), while the correlation coefficient of the overall BIC and CES-D was 0.62. Correlation between the BIC and ZBI, a preexisting care burden scale, was high (r = 0.84), while that with the time spent on providing care was 0.47. The ICC (Intraclass correlation coefficient) by test-retest reliability was 0.83, and 0.68 to 0.80 by individual domain. CONCLUSION: These results show that the BIC, a new care burden scale comprising 11 items, is highly reliable and valid.

[Non-persistent "doll phenomenon" in a patient with right thalamic infarction].

An 81-year-old right-handed woman was admitted because of acute dysarthria and left hemiparesis. She had lived herself without aids until the admission. On neurological examination she was confused and disoriented. She was ambulant, but had mild dysarthria and mild left hemiparesis. Neuropsychological tests showed severe impairment of memory, mild impairment of visual cognition, decreased fluency of word recall and mild paramnesia, but no acalculia, agraphia, aphasia or apraxia. MRI of the brain showed small infarction in the right anterior thalamus. 123I-IMP SPECT demonstrated a decrease in CBF of the thalamus, basal ganglia and frontal lobe on the right. During admission, she always played with a doll as if she took it as a real baby. This peculiar symptom. "doll phenomenon" continued for approximately three months later. The "doll phenomenon" usually appears in demented patients with diffuse mental deterioration or dysfunction of the frontal lobe. The present patient had not been demented until the onset of the thalamic infarction, and disturbance of cognition caused by the right thalamic infarction probably produced the "doll phenomenon".

[Bradykinetic utterances and monopitch speech in patients with Parkinson's disease].

We compared vocalization and speech of 20 patients with Parkinson's disease with those of 24 healthy volunteers using acoustic analysis. The time from the beginning of pronunciation of "a" to the maximum amplitude was significantly longer in the Parkinson group than in the healthy group. In a reading aloud test using a short sentence "o-te-ra-ni-o-ba-ke-ga-de-ta (a ghost appeared in a temple)", the coefficient of variation of the mean fundamental frequency for each syllable was significantly smaller in the Parkinson group. In addition, the Parkinson group showed few changes in the fundamental frequency of the each syllable through the whole sentence, which was spoken in a monopitch pattern. However, there were no differences between the Parkinson group and the healthy volunteers in the time that each syllable was sustained and in the length of syllables. These results suggest that patients with Parkinson's disease have bradykinetic utterance. In reading aloud the short sentence, the tone of each syllable was flat and the speech was monopitch lack articulation. The saccadic eye movements of 15 of the patients with Parkinson's disease were recorded using an electrooculogram in order to evaluate the correlation with bradykinetic utterances. Although monopitch speech and bradykinetic utterances were correlated, the bradykinetic saccadic eye movements and bradykinetic utterances were not correlated.

[Case of cerebral venous thrombosis secondary to Protein S gene abnormality first diagnosed as aseptic meningitis].

A 28-year-old man admitted to our hospital because of severe neck pain, headache, fever and vomiting. He was alert and had no neurological deficit except for nuchal stiffness. Cerebrospinal fluid (CSF) examination showed elevated mononuclear cell counts (68/mm(3)) and protein levels (300 mg/dl). He was diagnosed as having aseptic meningitis and was thereby treated. Two days later, he manifested seizure and on the next day, severe cerebral hemorrhage occurred in the left parietal lobe and decompression surgery was performed. Cerebral venous thrombosis was strongly indicated by operative findings, cerebral angiography and retrospective assessment of MRI images. Genetic testing revealed a novel mutation (p.Cys449Tyr) combined by Protein S Tokushima mutation (p.Lys196Glu) which is frequently observed in Japanese. Possibility of CVT should be noted, even when a patient exhibits clinical symptoms and CSF findings compatible with a diagnosis of aseptic meningitis.

Neuro-Sweet disease: report of the first autopsy case.

BACKGROUND: Neuro-Sweet disease is a rare condition of central nervous involvement accompanied by cutaneous Sweet lesions. Neuropathological changes in neuro-Sweet disease are unknown. OBJECTIVE: To describe post-mortem findings of the first case of neuro-Sweet disease. RESULTS: A 44-year-old Japanese man developed recurrent episodes of cerebral and brainstem encephalitis with cutaneous Sweet lesions from the age of 34 years. His HLA typing was B54 and Cw1, and the symptoms and MRI abnormalities markedly subsided following corticosteroid therapy. Histologically, there were multiple lesions of perivascular cuffing of small venules by macrophages without vasculitis in the thalamus, temporal lobe, basal ganglia, pons, leptomeninges or ventricular ependym. CONCLUSIONS: THE CORE NEUROPATHOLOGICAL FINDINGS WERE: perivascular cuffing around particularly small veins; absence of granulomatous or necrotic angitis; mainly macrophage infiltration; and the thalamus being most affected. In the present case, the diagnosis of neuro-Sweet disease was made by skin biopsy 5 years after the onset of the central neuron system symptoms. We should pay more attention to skin lesions in steroid responsive recurrent encephalitis in patients who are HLA-B54 or Cw1 positive.